16-87604287-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-CCTGCTGCTGCTGCTGCTGCTG

Variant names:

• chr16-87604287-CCTGCTGCTG-C
• rs71156237
• NM_020655.4:c.382+793_382+801delCTGCTGCTG

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3 BS1 BS2

The NM_001271604.4(JPH3):​c.464_472delCTGCTGCTG​(p.Ala155_Ala157del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 1,432,756 control chromosomes in the GnomAD database, including 377 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.022 (51 hom., cov: 0)
  • Exomes 𝑓: 0.026 (326 hom.)
• Consequence: JPH3 NM_001271604.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966
• Publications: 1 publications found

Genes affected

JPH3 (HGNC:14203): (junctophilin 3) Junctional complexes between the plasma membrane and endoplasmic/sarcoplasmic reticulum are a common feature of all excitable cell types and mediate cross talk between cell surface and intracellular ion channels. The protein encoded by this gene is a component of junctional complexes and is composed of a C-terminal hydrophobic segment spanning the endoplasmic/sarcoplasmic reticulum membrane and a remaining cytoplasmic domain that shows specific affinity for the plasma membrane. CAG/CTG repeat expansion from normally 6-28 repeats to 40-59 repeats in the 3' UTR of this gene have been associated with Huntington disease-like 2 (HDL2). This gene is a member of the junctophilin gene family. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2016]

JPH3 Gene-Disease associations (from GenCC):

• Huntington disease-like 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001271604.4
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0219 (3281/150046) while in subpopulation NFE AF = 0.0295 (1992/67442). AF 95% confidence interval is 0.0285. There are 51 homozygotes in GnomAd4. There are 1599 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3281 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271604.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH3	NM_020655.4	MANE Select	c.382+793_382+801delCTGCTGCTG		intron	N/A	NP_065706.2
	JPH3	NM_001271604.4		c.464_472delCTGCTGCTG	p.Ala155_Ala157del	disruptive_inframe_deletion	Exon 2 of 2	NP_001258533.1
	JPH3	NM_001271605.3		c.*162_*170delCTGCTGCTG		3_prime_UTR	Exon 2 of 2	NP_001258534.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH3	ENST00000284262.3	TSL:1 MANE Select	c.382+793_382+801delCTGCTGCTG		intron	N/A	ENSP00000284262.2
	JPH3	ENST00000301008.5	TSL:1	n.724_732delCTGCTGCTG		non_coding_transcript_exon	Exon 2 of 2
	JPH3	ENST00000537256.5	TSL:2	n.96+2391_96+2399delCTGCTGCTG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 3279 AN: 149940 Hom.: 51 Cov.: 0

Gnomad AFR AF: 0.00868

Gnomad AMI AF: 0.00889

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.00348

Gnomad EAS AF: 0.00591

Gnomad SAS AF: 0.00488

Gnomad FIN AF: 0.0550

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0295

Gnomad OTH AF: 0.0161

GnomAD4 exome AF: 0.0257 AC: 33023 AN: 1282710 Hom.: 326 AF XY: 0.0248 AC XY: 15673 AN XY: 632926

African (AFR) AF: 0.00653 AC: 185 AN: 28324

American (AMR) AF: 0.0112 AC: 362 AN: 32398

Ashkenazi Jewish (ASJ) AF: 0.00222 AC: 48 AN: 21658

East Asian (EAS) AF: 0.00420 AC: 101 AN: 24072

South Asian (SAS) AF: 0.00514 AC: 400 AN: 77824

European-Finnish (FIN) AF: 0.0221 AC: 650 AN: 29368

Middle Eastern (MID) AF: 0.0107 AC: 54 AN: 5062

European-Non Finnish (NFE) AF: 0.0298 AC: 30211 AN: 1012944

Other (OTH) AF: 0.0198 AC: 1012 AN: 51060

GnomAD4 genome AF: 0.0219 AC: 3281 AN: 150046 Hom.: 51 Cov.: 0 AF XY: 0.0218 AC XY: 1599 AN XY: 73212

African (AFR) AF: 0.00871 AC: 354 AN: 40666

American (AMR) AF: 0.0170 AC: 257 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.00348 AC: 12 AN: 3448

East Asian (EAS) AF: 0.00593 AC: 30 AN: 5062

South Asian (SAS) AF: 0.00488 AC: 23 AN: 4710

European-Finnish (FIN) AF: 0.0550 AC: 567 AN: 10300

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0295 AC: 1992 AN: 67442

Other (OTH) AF: 0.0159 AC: 33 AN: 2076

Alfa AF: 0.0185 Hom.: 316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs71156237; hg19: chr16-87637893; COSMIC: COSV108775487; COSMIC: COSV108775487;